Although it has been well documented that initiation of hemostasis involves the adhesion of platelets to collagen fibers, the mechanism whereby this reaction occurs and the formation of a platelet plug is triggered is still unknown. The interaction between platelets and collagen is of prime importance in the study of hemostasis, thrombosis, intravascular coagulation, atherosclerosis, and similar diseases of the circulatory system, and many investigators have pursued this problem. We plan to approach these studies from a different point of view, applying a variety of physical-chemical techniques to interactions with platelets of native, as well as chemically or enzymically modified, collagen or of synthetic collagen-like polypeptides. We hope thereby to elucidate the function of collagen in the first and subsequent steps of hemostasis, to determine the required sequence, structure, or functional groups, to deduce the mechanism of the reactions, and to develop ways in which the latter may be perturbed. Such knowledge should benefit investigations of hemostasis, thrombosis, atherosclerosis, intravascular coagulation, and similar diseases of the circulatory system; it should also be useful in the development of treatments for collagenolytic diseases in which the breakdown of collagen itself plays a role, such as rheumatoid arthritis. Once the function of collagen in platelet adhesion and aggregation is understood it should be possible to design artificial systems, for example, to facilitate the formation of platelet plugs in some hemorrhagic conditions, or to, alternatively, prevent their formation in cases where excessive or undesired coagulation is a medical problem.